FAB Classification of the Acute Myeloid Leukemias PDF

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FAB Classification of the Acute Myeloid Leukemias ( ANLLs) Learning Outcomes List eight diseases that are classified as acute myeloproliferative disorders. (M0-M7) Create a chart that could be used to differentiate the various FAB classifications of the acute myelogenous leukemias including unique clinical features, laboratory features, chromosomal abnormalities, and therapy. Compare the FAB classification of acute myelogenous leukemia with the WHO classification. (number of blast, Who 20%, 30% for FAB) M0: AML minimal differentiated- stem cell leukemia Morphology: Undifferentiated leukemic blasts with myeloid immunophenotype React with myeloid markers React with at least one myeloid marker (CD13, 33 , 34 or 117).

M0: AML minimal differentiated Cytochemical Rxn: Peroxidase & SBB: 0 to 2% positive rxn. Non-Specific Esterase: 0 to 2% positive rxn (Buterase) CD Markers: CD 13, CD 33, CD 34, CD117 (strong) M1: AML without Maturation (myeloblast origin) Morphology: Marrow leukemia cells are primarily myeloblasts (90%) with no or minimal azurophilic granules. Rare Auer Rod seen. (Auer rods seen 50% of time)

come out of bone marrow in sheet high wbcs M1: AML without Maturation Cytochemical Rxn: Peroxidase & SBB: > 3% positive rxn. NSE: < 20% positive rxn. Cytogenetics:  Trisomy 8  t(9,22)= philadenpha chromosome CD Markers: CD 13, CD 33, CD 34, CD117 (strong) M2: Myeloid with Maturation (AML with maturation) cell beyond the myeoblasts Morphology: Leukemic cells show prominent maturation beyond the myeloblast stage. 50% combination of promyelocytes and myeloblasts. (> 10% of the cells have matured beyond the promyelocyte stage). Auer rods may be seen (common in M2 than M1 b/c more maturation of blasts)

many blasts, M2: AML with Maturation Cytochemical Rxn: MORE MATURE THE BLASTS IS, THE MORE STAIN IT PICK UP Peroxidase and SBB: > 50% positive rxn. NSE: < 20% positive rxn. Chromosomal Abn: t(8;21): CD 13, CD 33, CD 117 M3: Acute Promyelocytic Leukemia (APL) Morphology: Abnormal, hypergranular promyelocytes dominate; auer rods easily found and occasionally seen in bundles (faggot cells).

Increased incidence of DIC: promyelocytes stimulate the thrombotic cascade

M3: Acute Promyelocytic Leukemia (APL) Cytochemical Rxn: Peroxidase & SBB: Nearly 100% positive rxn. NSE: Variable Chromosome Abnormality: t(15;17) 15q+, 17q- (15 long arm gain, 17 long arm lost)

This translocation forms the PML/RAR α gene CD Markers: CD 13, 33 and 117 Treatment: ATRA: all trans rycnoic acid, this target the cells mutations and make the cells to mature M3m: Microgranular variant of M3 Morphology: Indistinct granules; nucleus often reniform or bilobed; look like monoblasts Increased incidence of DIC Stain match with M3 M3m Cytochemical Rxn , Chromosomal Abn and CD Markers: Same as M3

M4: Myelomonocytic (AMML) (Naegeli type) Morphology: Both monocytic (monoblasts, promonos, monos) and myeloid differentiation (maturation beyond the myeloblast stage) is seen. M4: AMML Cytochemical Rxn:

Peroxidase and SBB: 20 - 80% positive rxn, NSE: 20 - 80% positive rxn. CD Markers: CD 11b, CD 13, CD 14, CD 33, CD 117

M4eo: M4 with bone marrow eosinophilia Morphology: Similar to M4 with marrow eosionophila Cytochemical Rxn: Same as M4 Chromosomal abn: 16q inversion or deletion

M5a: Monoblastic Leukemia, (AmoL), (Schilling’s type) Morphology: Monoblasts predominate

M5a: AMoL Cytochemical Rxn. Peroxidase & SBB: variable NSE: > 80% positive rxn. Chromosomal Abnormality: Del (11) or t(9;11) 9p+; 11qCD Markers: CD 11b , CD 14, CD 33 Will have Increased serum muramidase levels (monocytic cells). M5b: Acute Monocytic Leukemia, (AMoL with differentiation) Morphology: Predominantly promonocytes in b.m. and more pronounced maturation in peripheral blood.

M5b: Acute monocytic -AmoL with differentiation Cytochemical rxn and CD markers.: same as M5a

M6: Erythroleukemia (AEL) Morphology: Dysplastic erythroblasts with multinucleated cytoplasmic budding; vacuolation, and megaloblastoid changes; will see an increase in myeloblasts and promyelocytes in b.m. 2 cell line abnormal: red cell line ad myeloid cell line

M6: Erythroleukemia Cytochemical Rxn: Peroxidase and SBB: > 3% positive rxn. NSE: Variable Cells are strongly PAS + CD Markers: CD 71+ (Glycophorin A) (differ with M1) M7: Megakaryoblastic Leukemia (AMkL) Morphology: Megakaryoblasts with cytoplasmic projections Electron microscopy and immunochemical stains necessary for diagnosis M7: AMkL Cytochemical Rxn: Peroxidase and SBB: < 3% positive rxn. NSE: Variable Platelet Peroxidase stain (PPO): Positive rxn. CD markers: CD 41, CD 42 and CD 61

Case Study 32 year old Hispanic woman Presents to physician with fatigue, easy bruising, and heavy menstrual bleeding. Medical History: Hypertension Chronic sinusitis = leukemia Mitral valve prolapse Case Study Physical Exam: Many small ecchymoses (bruises) noted over her lower and upper extremities. No splenomegaly or lymphadenopathy noted. Case Study Laboratory Features: WBC: 2,000/ul, low RBC: 4,500,000/ul, low Hgb: 14.0 g/dl Hct: 39.7 % MCV: 86.7 fl MCHC: 35.5 % Platelet count: 47,000/ul, low Case Study Coagulation Studies: Protime: 14.1 seconds (high) Normal ( 9.2-12.6 secs.) D-dimer: 6.0 mg/L (pos) Normal (0 -2.4 mg/L) Protime= how long it take to clot Case Study Peripheral Blood Cell Differential: Segs: 23% Lymphs: 33%

Monos: 13% Eosinophils: 1% Blasts: 30% Case Study Peripheral Blood Photos Case Study Bone Marrow Differential: Myeloblasts: 53% Promyelocytes: 16% Myelocytes: 2% Metamyelocytes: 1% Bands: 3% Segs: 1% Monos 1% NRBCs: 14% Case Study Bone Marrow Photos: Case Study Additional Lab Findings: Myeloperoxidase stain: 97% positive NSE stain: 0% positive Choloracetate stain: 90% positive CD13: 98% positive (myeloid marker) CD33: 96% positive (myeloid marker) CD 117: 96% positive (myeloid marker) Case Study

46XX, t(15;17)

Chromosome (q22;q21.1) Analysis

Case Study

Molecular Genetics Analysis: SHE HAS M3m

FISH Analysis: Positive for the PML/RARα gene rearrangement PCR: Positive for the t(15;17)PML-RARα translocation. alpha translocatio...